The use of L-dihydroxyphenylalanine (L-Dopa) in the treatment of brain diseases was originally predicted on the assumption that this amino acid would be converted to dopamine, which could then be utilized as a neurotransmitter in the basal ganglia. Studies here and elsewhere have shown that only a very small fraction of administered L-Dopa has this fate; moreover, L-Dopa causes profound changes in brain neurons containing norepinephrine and serotonin, in brain methylation reactions, and in the mechanisms of brain protein synthesis (i.e., polysome aggregation and amino acid metabolism). It seems possible that the effects of L-Dopa on mood and motivation may be mediated by actions unrelated to dopamine synthesis. Studies are proposed to characterize the effects of L-Dopa on brain methylation reactions, and to determine whether its own conversion to dopamine and norepinephrine can be enhanced if its in vivo methylation is blocked. We also hope to determine whether the Dopa-induced disaggregation of brain polysomes is mediated by Dopa itself, catecholamines formed from it, its O-methylated product 3-0-methyl Dopa, or by the depletion of brain S-adenosyl- methionine. We will examine the sources of methyl groups (i.e., methionine, S-adebosyl-methionine, folates) in brain, and the contributions of diet and de novo synthesis to brain methionine. We have recently found that experimental ischemic stroke (caused by ligating the middle cerebral artery in monkeys, or the common carotid in gerbils) depletes ipsilateral brain dopamine. We will now examine the fate and actions of this released dopamine, and explore the possibility that therapies designed to raise or to block the actions of brain dopamine might have some place in the chronic or acute therapy of cerebro-vascular diseases.